1262 Part VII / Development and the Emergence of Behavior
Figure 51–1 The role of the SRY gene in sex determination
in humans.SRY, the sex-determining locus (blue domain),
resides on the nonhomologous region of the short arm of the
Y chromosome. The presence of SRY is determinative for male
differentiation in many mammals, including primates and most
rodents. Normally X- or Y-bearing sperm fertilize an oocyte to
generate XX females or XY males, and the resulting phenotypic
sex is concordant for the chromosomal sex. Rarely, SRY trans-
locates to the X chromosome or an autosome (not shown). In
such cases, XX
SRY
offspring are phenotypically male, whereas
XY
ΔSRY
offspring (the Δ indicating a gene deletion) are pheno-
typically female. (Adapted from Wilhelm, Palmer, and Koopman
2007.)
program appears to be the default mode; patterning
genes prime the body and gonads to develop along
female-specific pathways. The SRY gene encodes a
transcription factor that regulates expression of genes,
some of which prevent execution of the default pro-
gram and initiate the process of male gonadal differ-
entiation. One of the best-studied targets of the SRY
transcription factor is another transcription factor,
SOX9, which is required for differentiation of the tes-
tes. Thus, SRY initiates a cascade of inductive inter-
actions that ultimately lead to male-specific gonad
development.
Gonads Synthesize Hormones That Promote
Sexual Differentiation
The chromosomal complement of the embryo directs
sexual differentiation of the gonads, and in turn, the
gonads determine the sex-specific features of all organs
of the body, including the nervous system. They do this
by secreting hormones. Gonadal hormones have two
major roles. Their developmental role is traditionally
referred to as organizational because the early effects of
hormones on the brain and the rest of the body lead to
major, generally irreversible, aspects of cell and tissue
differentiation. Later, some of the same hormones trig-
ger physiological or behavioral responses. These influ-
ences, generally termed activational, are reversible.
One example of an organizational role of gonadal
hormones is seen in the differentiation of structures
that connect the gonads to the external genitalia. In
males, the Wolffian duct gives rise to the vas deferens,
the seminal vesicles, and the epididymis. In females,
the Müllerian duct differentiates into the oviduct, the
uterus, and the vagina (Figure 51–2). Initially, both
female (XX) and male (XY) embryos possess Wolffian
and Müllerian ducts. In males, the developing testes
secrete a protein hormone, the Müllerian inhibiting
substance (MIS), and a steroid hormone, testosterone.
MIS leads to a regression of the Müllerian duct, and
testosterone induces the Wolffian duct to differentiate
into its mature derivatives. In females, the absence of
MIS permits the Müllerian duct to differentiate into its
adult derivatives, and the absence of circulating tes-
tosterone causes the Wolffian duct to resorb. Thus, the
Y chromosome overrides a female default program to
generate male gonads, which in turn secrete hormones
that override a female default program of genital
differentiation.
The action of MIS is largely confined to embryos,
but steroid hormones exert effects throughout life—
that is, they also have activational roles at later stages.
All of the steroid hormones derive from cholesterol
(Figure 51–3). The sex steroids can be divided into
androgens, which generally promote male character-
istics, and the estrogens plus progesterone that pro-
mote female characteristics. The testes produce mostly
the androgen testosterone, while the ovaries produce
mostly progesterone and an estrogen, 17-β-estradiol.
The menstrual cycle is a good example of the activa-
tional function of estrogen and progesterone.
A glance at the metabolic relationships among
steroid hormones (Figure 51–3) reveals a surprise.
The female hormone progesterone is the precursor of
the male hormone testosterone, and testosterone is the
direct precursor of the female hormone 17-β-estradiol.
Thus, the enzymes that convert one hormone to the
other control not only the level of the hormone but
also the “sign” (male or female) of the hormonal effect.
Aromatase, the enzyme that converts testosterone to
estradiol, is present at high levels in the ovaries but
not in the testes. Differential expression of aromatase
is the reason for sexual dimorphism in circulating tes-
tosterone and estrogen. Aromatase is also expressed in
various regions of the brain (Figure 51–4A), and many
of the effects of testosterone on neurons are thought
to occur after its conversion to estrogen. Testosterone
雌性化
表现型
雄性化
表现型
受精
正常交叉 异常交叉
XX
SRY
XY
∆SRY
XX XY
Kandel-Ch51_1260-1284.indd 1262 20/01/21 2:57 PM
雄性化
表现型
雌性化
表现型